Search

The elevated risk of severe COVID-19 outcomes in patients with diabetes underscores the need for effective predictive tools. This study aimed to assess the predictive accuracy of APACHE II, CURB-65, SOFA, and NEWS2 scores at critical time points in diabetic patients diagnosed with COVID-19, aiming to guide early and potentially life-saving interventions. In a prospective cohort study conducted from January 2021 to December 2023, adult patients with type 1 or type 2 diabetes and confirmed SARS-CoV-2 infection were evaluated. Clinical scores were calculated at admission and five days post-symptom onset, with data analyzed using receiver operating characteristic (ROC) curves and logistic regression to determine areas under the curve (AUC) and hazard ratios (HR) for severe outcomes. Among the 141 diabetic patients studied, ROC analysis revealed high AUC values for SOFA (0.771 at admission, 0.873 at day five) and NEWS2 (0.892 at admission, 0.729 at day five), indicating strong predictive accuracy for these scores. The APACHE II score's AUC improved from 0.698 at admission to 0.806 on day five, reflecting worsening patient conditions. Regression analysis showed significant HRs associated with exceeding threshold scores: The SOFA score HR at day five was 3.07 (95% CI: 2.29-4.12, p < 0.001), indicating a threefold risk of severe outcomes. Similarly, the APACHE II score showed an HR of 2.96 (95% CI: 2.21-3.96, p < 0.001) at day five, highlighting its utility in predicting severe disease progression. The SOFA and NEWS2 scores demonstrated excellent early predictive accuracy for severe COVID-19 outcomes in diabetic patients, with significant AUC and HR findings. Continuous score monitoring, especially of APACHE II and SOFA, is crucial for managing and potentially mitigating severe complications in this vulnerable population. These tools can effectively assist in the timely escalation of care, thus potentially reducing morbidity and mortality among diabetic patients during the COVID-19 pandemic.

Objective: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes., Methods: A total of 642 study participants with CRS were prospectively enrolled and self-selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded pre- and post-treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φ c ) with 95% confidence interval (CI) were calculated., Results: A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φ c  = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT-22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF-6D values (Rs = -0.20; 95% CI: -0.27, -0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within-subject improvement, or achievement of >1 minimal clinically important difference, in SNOT-22 or SF-6D scores after treatment were found., Conclusions: Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease-specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Key Points: AI-based CT sinus analysis may have advantages over visual based systems, for example, Lund-Mackay score. Here, we show multi-institutional validation of an AI algorithm using novel OMC classification. Significant, robust correlations are seen between algorithm outputs and clinical outcomes., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies., Study Design: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations., Setting: An online questionnaire was distributed in July 2023., Methods: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1., Results: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case., Conclusion: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown., Objective: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS)., Methods: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 μm and <10 μm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (β) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed., Results: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P   =  .01) and after covariate adjustment with multivariate analysis ( B   =  1.06, 95% CI: 0.001, 2.14, P   =  .05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively., Conclusion: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.M.B: Grant support from CF Foundation and from the International Society of Inflammation and Allergy of the Nose, unrelated to this work. Garner Health, consultant, equity. Honoraria from Rockpointe and Trinity Sciences. J.A.A: GlycoMira consultant, equity. GSK speaker panel. OptiNose consultant, Medtronic consultant. Z.M.S: Lyra, Optinose, Regeneron consultant. Medical director Healthy Humming.

Purpose: To evaluate microbiological cultures of cataract surgical devices and products that were reused for multiple cases., Setting: Aravind Eye Hospital, Pondicherry, Tamil Nadu, India., Design: Prospective cohort study., Methods: Samples from multiple surgical instruments and products that were reused for consecutive cataract surgeries underwent bacterial and fungal cultures and were monitored alongside positive controls for 7 days. This included instruments that were processed using immediate use steam sterilization (IUSS) between cases (e.g., surgical cannulas, syringes, phacoemulsification and coaxial/bimanual irrigation and aspiration (IA) tips, phacoemulsification and IA sleeves) (Group 1), instruments that were used without sterilization between cases (e.g., phacoemulsification tubing/handpieces, coaxial IA handpieces) (Group 2) and the residual (unused) fluid from balanced salt solution bags after being used for multiple patients (Group 3)., Results: 3,333 discrete samples were collected from all 3 product groups that were reused across multiple patients. In all collected samples, no bacterial or fungal growth was observed. Of the 3,241 cataract surgeries that utilized reused and IUSS-sterilized instruments alongside instrument sets cultured on the same day and balanced salt solution bags shared across multiple patients, no eyes developed endophthalmitis over a 6-week follow-up period., Conclusion: Bacterial or fungal growth was not found in extensive microbiological cultures of IUSS-sterilized ophthalmic surgical instruments, and cataract surgical products that were reused in multiple patients. This microbiological data complements clinical endophthalmitis data from 2 million consecutive cases at the Aravind Eye Hospital, suggesting that their instrument and surgical supply processing practices may allow for safe and sustainable ophthalmic care., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures., Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES)., Results: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures., Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes., (© 2023 ARS‐AAOA, LLC.)

Background: Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS-specific disease severity. We assessed the impact of air pollutants on sinonasal-specific and general quality-of-life (QOL) measures in a multi-institutional cohort of patients with CRS., Methods: Participants with CRS were prospectively enrolled in a cross-sectional study and self-selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association., Results: A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD] ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT-22 or SF-6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, [95% confidence interval {CI}: 0.003, 0.234]; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m 3 ) did not correlate with change in total SNOT-22 or SF-6D scores after treatment. Nevertheless, sulfur dioxide (SNOT-22: ρ = -0.121 [95% CI: -0.210, -0.030]; p = 0.007; SF-6D: ρ = 0.095 [95% CI: 0.002, 0.186]; p = 0.04) and carbon monoxide (SNOT-22: ρ = -0.141 [95% CI: -0.230, 0.050]; p = 0.002) exposure did correlate with these outcome measures., Conclusion: Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Introduction: Females, versus males, have shown a slower decline in smoking prevalence, greater smoking-related mortality and morbidity, and tend to have more difficulty achieving and maintaining abstinence. Identifying sex-specific risk factors is needed to improve outcomes. Though ovarian hormones have been evaluated for their role in smoking and relapse, measures tend to be static and infrequent, failing to capture the influence of increasing or decreasing levels., Aims and Methods: The present study evaluated the effect of static and fluctuating levels of ovarian hormones (ie, progesterone, estradiol, and estrogen to progesterone [E/P] ratio) on stress reactivity, cigarette craving, and smoking during a laboratory relapse paradigm. Female participants (assigned female at birth) reporting daily cigarette smoking (N = 91, ages 18-45) were recruited from the community. Participants provided daily salivary ovarian hormone levels leading up to a laboratory session, in which stress was induced and stress reactivity, cigarette craving, latency to smoke, and ad-libitum smoking were measured., Results: Static levels of estradiol were associated with stress reactivity (β = 0.28, SE = 0.13) and static E/P ratio was associated with smoking in the laboratory (HR = 1.4). Preceding 3-day changes in estradiol and E/P ratio, but neither static levels nor preceding 3-day changes in progesterone were associated with stress reactivity, cigarette craving, or smoking in a relapse paradigm., Conclusions: Ovarian hormones are among several sex-specific factors involved in the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood., Implications: Findings of the present study provide novel information regarding the role of ovarian hormones among female participants who smoke daily in stress reactivity and smoking in the context of a laboratory relapse paradigm and highlight several avenues for future research. We found that same-day estradiol levels were associated with increased subjective stress reactivity and same-day estrogen to progesterone ratio was associated with increased likelihood of smoking in a relapse paradigm. Ovarian hormones are among several sex-specific factors contributing to the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The study aimed to investigate otolaryngologists' knowledge, trust, acceptance, and concerns with clinical applications of artificial intelligence (AI)., Methods: This study used mixed methods with survey and semistructured interviews. Survey was e-mailed to American Rhinologic Society members, of which a volunteer sample of 86 members responded. Nineteen otolaryngologists were purposefully recruited and interviewed until thematic saturation was achieved., Results: Seventy-six respondents (10% response rate) completed the majority of the survey: 49% worked in academic settings and 43% completed residency 10 or fewer years ago. Of 19 interviewees, 58% worked in academic settings, and 47% completed residency 10 or fewer years ago. Familiarity : Only 8% of survey respondents reported having AI training in residency, although 72% had familiarity with general AI concepts; 0 interviewees had personal experience with AI in clinical settings. Expected uses : Of the surveyed otolaryngologists, 82% would use an AI-based clinical decision aid and 74% were comfortable with AI proposing treatment recommendations. However, only 44% of participants would trust AI to identify malignancy and 53% to interpret radiographic images. Interviewees trusted AI for simple tasks, such as labeling septal deviation, more than complex ones, such as identifying tumors. Factors influencing AI adoption: 89% of survey participants would use AI if it improved patient satisfaction, 78% would be willing to use AI if experts and studies validated the technologies, and 73% would only use AI if it increased efficiency. Sixty-one percent of survey respondents expected AI incorporation into clinical practice within 5 years. Interviewees emphasized that AI adoption depends on its similarity to their clinical judgment and to expert opinion. Concerns included nuanced or complex cases, poor design or accuracy, and the personal nature of physician-patient relationships., Conclusion: Few physicians have experience with AI technologies but expect rapid adoption in the clinic, highlighting the urgent need for clinical education and research. Otolaryngologists are most receptive to AI "augmenting" physician expertise and administrative capacity, with respect for physician autonomy and maintaining relationships with patients., Level of Evidence: Level VI, descriptive or qualitative study., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process., Conclusions: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Key Points: Bacterial composition is uniform in the sinuses of postviral olfactory dysfunction patients. Significant reduction of genus Corynebacterium in PVOD patients compared to controls., (© 2023 ARS-AAOA, LLC.)

Background: Overcoming non-standardization, vagueness, and subjectivity in sinus CT radiology reports is an ongoing need, particularly in keeping with data-driven healthcare initiatives. Our aim was to explore otolaryngologists' perceptions of quantitative objective disease measures as enabled by AI-based analysis, and determine preferences for sinus CT interpretation., Methods: A multi-methods design was used. We administered a survey to American Rhinologic Society members and conducted semi-structured interviews with a purposeful sample of otolaryngologists and rhinologists from varying backgrounds, practice settings and locations during 2020-2021. Interview topics included sinus CT reports, familiarity with AI-based analysis, and potential requisites for its future implementation. Interviews were then coded for content analysis. Differences in survey responses were calculated using Chi-squared test., Results: 120 of 955 surveys were returned, and 19 otolaryngologists (8 rhinologists) were interviewed. Survey data revealed more trust in conventional radiologist reports, but that AI-based reports would be more systematic and comprehensive. Interviews expanded on these results. Interviewees believed that conventional sinus CT reports had limited utility due to inconsistent content. However, they described relying on them for reporting incidental extra-sinus findings. Reporting could be improved with standardization and more detailed anatomical analysis. Interviewees expressed interest in AI-derived analysis given potential for standardization, although they desired evidence of accuracy and reproducibility to gain trust in AI-based reports., Conclusions: Sinus CT interpretation has shortcomings in its current state. Standardization and objectivity could be aided with deep learning-enabled quantitative analysis, although clinicians desire thorough validation to gain trust in the technology prior to its implementation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Statement of Problem: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD., Methods: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale., Results: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log., Conclusions: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Introduction: In chronic rhinosinusitis (CRS), a complex pathophysiology results from varied pro-inflammatory stimuli but is consistently characterized by classic cellular, molecular, and microbial alterations. Normally, endogenous specialized pro-resolving mediators (SPM) actively promote resolution of inflammation through numerous pathways, including those involved in host antimicrobial defense. However, these pathways appear to be disrupted in CRS., Areas Covered: This paper describes features of CRS in the context of chronic tissue inflammation, and potential mechanisms by which specialized pro-resolving mediators promote active resolution of tissue inflammation., Expert Opinion: Temporal phases of resolution must be tightly regulated to successfully resolve inflammation in CRS while preserving tissue functions such as barrier maintenance and special sensory function. Dysregulation of SPM enzymatic pathways has been recently shown in CRS and is associated with disease phenotypes and microbial colonization patterns. Current research in animal models and in vitro human cell culture, as well as human dietary studies, demonstrate relevant changes in cell signaling with lipid mediator bioavailability. Further clinical research may provide insight into the therapeutic value of this approach in CRS.

Purpose: To evaluate the visual and surgical outcomes of cataract surgery in patients with posterior polar cataract (PPC) and to evaluate the benefits of preoperative anterior segment optical coherence tomography (AS-OCT)., Methods: This was a retrospective, single-center study. Case records of patients diagnosed with PPC who underwent cataract surgery either by phacoemulsification or manual small-incision cataract surgery (MSICS) from January to December 2019 were analyzed. Data collected include demographic details, preoperative best corrected visual acuity (BCVA), AS-OCT, type of cataract surgery, intraoperative and postoperative complications, and visual outcome at 1-month follow-up., Results: One hundred patients were included in the study. Preoperative posterior capsular defect was noted on AS-OCT in 14 patients (14%). Seventy-eight underwent phacoemulsification and 22 underwent MSICS. Intraoperatively, posterior capsular rupture (PCR) was seen in 13 patients (13%) and cortex drop was noted in one among them (1%). Out of 13 PCRs, 12 were found to have posterior capsular dehiscence preoperatively in AS-OCT. The sensitivity of AS-OCT for detecting posterior capsule dehiscence was 92.3% and specificity was 97.7%. The positive predictive value and negative predictive value were 85.7% and 98.8%, respectively. There was no significant difference in the incidence of PCR between phacoemulsification and MSICS (P = 0.475). The mean BCVA at 1 month was found to be better with phacoemulsification than MSICS (P = 0.004)., Conclusion: Preoperative AS-OCT has excellent specificity and negative predictive value in identifying posterior capsular dehiscence. It thus helps to plan the surgery and counsel patients appropriately. Both phacoemulsification and MSICS provide good visual outcome with similar complication rates., Competing Interests: None

Small traumatic iridodialysis (ID) may be asymptomatic, but large ones usually cause polycoria and corectopia, leading to symptoms like diplopia, glare, and photophobia. The management of ID, including medical and surgical methods, depends upon the patient's symptoms. Mild glare and diplopia can be treated either with atropine, antiglaucoma medications, tinted spectacles, colored contact lens, or corneal tattooing, but extensive IDs require surgical options. The surgical techniques are challenging due to the iris texture and the damage encountered during the primary surgery, the narrow anatomical workspace for repair, and the associated surgical complications. Numerous techniques have been described by several authors in the literature; each has its advantages and disadvantages. All the procedures described previously involve conjunctival peritomy, scleral incisions, and suture knots and are time consuming. Here, we report a novel transconjunctival, intrascleral, knotless, and ab-externo, double-flanged technique for repair of large ID with a 1-year follow-up., Competing Interests: None

Background: Antagonists to the P2X purinergic receptors on airway sensory nerves relieve refractory or unexplained chronic cough (RCC/UCC) but can evoke unwanted dysgeusias because the gustatory nerves innervating taste buds express this same family of receptors. However, the subunit composition of the P2X receptors in these systems may differ, with implications for pharmacological intervention of RCC/UCC. In most species, the extrapulmonary airway nerves involved in cough predominantly express P2X3 subunits that form homotrimeric P2X3 receptors. In contrast, most sensory nerves innervating taste buds in mice express both P2X2 and P2X3 subunits, so the majority of receptors in that system are likely P2X2/P2X3 heteromers., Methods: Since neural P2X subunit composition can differ across species, we used immunohistochemistry to test whether taste nerves in humans and rhesus macaque monkeys express both P2X2 and P2X3 as in mice., Results: In taste bud samples of fungiform papillae and larynx from humans and monkeys, all taste bud samples exhibited P2X3 + nerve fibres, but the majority lacked substantial P2X2 + . Of the 35 human subjects, only four (one laryngeal and three fungiform) showed strong P2X2 immunoreactivity in taste nerves; none of the rhesus monkey samples showed immunoreactivity for P2X2., Conclusions: These findings suggest that for most humans, unlike mice, taste buds are innervated by nerve fibres predominantly expressing only P2X3 homomeric receptors and not P2X2/P2X3 heteromers. Thus, antagonists specific for P2X3 homomeric receptors might not be spared from affecting taste function in RCC/UCC patients., Competing Interests: Conflict of interest: Since 2018, T. Hummel has performed research together with and received funding from Sony, Stuttgart, Germany; Smell and Taste Lab, Geneva, Switzerland; Takasago, Paris, France; Aspuraclip, Berlin, Germany; Baia Foods, Madrid, Spain; Frequency Therapeutics, Farmington, CT, USA; and Bayer Healthcare, Berlin, Germany. The remaining authors do not have conflicts of interests to disclose., (Copyright ©The authors 2023.)

Objective: Despite extensive research into chronic rhinosinusitis (CRS) epidemiology, presentation, and outcomes, there is scant knowledge on sex-specific differences. The objective of this study was to identify differences between male and female patients with CRS in baseline disease severity at presentation, choice for surgery vs continued medical treatment, and postoperative response., Study Design: We evaluated data on demographic and health characteristics, clinical objective disease measures, and sinus-specific and general health patient-reported outcome measures., Setting: Secondary analysis of prospective multicenter outcome study., Methods: Comparison of cohort characteristics and baseline and postoperative measures was performed with a t test, chi-square test of independence, or Fisher exact test. Within-subject improvement was compared between sexes with a linear mixed model., Results: Females reported worse quality of life on presentation and postsurgery, despite experiencing less severe disease by standard clinical measures. Overall, females and males showed similar within-subject improvement after surgery. However, certain quality of life domains and disease measures showed sex-specific improvement. Females demonstrated greater within-subject improvement in SF6D-derived health utility and the SNOT-22 ear and facial, psychological, and sleep subdomains, although this did not reach statistical significance for the overall cohort., Conclusion: Incorporating data on sex-specific differences may be important to personalize CRS treatment decision making. The discordance between patient-reported and clinical measures in CRS has been demonstrated in other pathologies and appears to be exaggerated by sex. Biological and psychological bases for sex-specific differences in CRS manifestations are an intriguing topic for further research., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Productivity loss and activity limitations due to chronic rhinosinusitis (CRS) are known to contribute to the significant economic and personal burden of disease. The purpose of this study was to assess productivity and activity impairment before and after endoscopic sinus surgery (ESS) for medically refractory CRS., Methods: This investigation was a prospective, multi-institutional, observational cohort study. Patients diagnosed with medically refractory CRS completed the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) questionnaire before surgery and approximately 6 months after the procedure. Factors associated with minimal clinical important differences (MCIDs) for productivity and activity impairment were identified., Results: A total of 279 study participants were screened for inclusion, of whom 176 (63.1%) with postoperative follow-up were included in the final cohort. Preoperative productivity and activity impairment were observed in 63.2% and 69.8% of the patients, respectively. Among these patients, postoperative improvement equaling at least 1 MCID was reported in both productivity (76.1%) and activity (76.4%) impairments. Multivariate regression identified sphenoidotomy (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.03-17.02) as the only factor associated with increased likelihood of productivity improvement, whereas septoplasty during ESS (OR, 8.45; 95% CI, 2.33-30.68) and migraine (OR, 0.35; 95% CI, 0.12-0.96) were associated with differential odds of activity improvement., Conclusion: CRS is associated with a substantial burden on productivity and activity that significantly improves after treatment with ESS. These data may facilitate improved patient counseling and shared decision-making regarding surgical management for CRS., (© 2022 ARS-AAOA, LLC.)

Background: Olfactory dysfunction (OD) can occur from a variety of etiologies. However, there are few reports examining whether varying etiologies have unique profiles of psychophysical testing that may provide insight into the pathophysiology of OD., Methods: Adults with chronic rhinosinusitis with and without nasal polyps (CRSwNP/CRSsNP) and healthy control adults with no sinus complaints underwent olfactory assessment with Sniffin' Sticks. Profiles of identification and discrimination were compared between CRS and non-CRS subjects across the spectrum of OD., Results: Normosmics with or without CRS identified apple, pineapple, and turpentine less frequently than expected (range 52%-68% correct). Hyposmics with CRS correctly identified orange more frequently than control hyposmics (83%-93% vs 68% for controls) with similar findings for rose. Hyposmics of all cohorts were unable to identify apple (26%). Discrimination profiles were similar across the spectrum of OD and between diagnostic groups., Conclusions: Identification and discrimination rates of specific odorants may provide unique information regarding the etiology of OD, however psychophysical testing is a complex interplay of olfactory and trigeminal function, the strength of target odorant, distractor choices, and familiarity with odorants.

Objective: Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life., Study Design: Prospective cohort., Setting: Academic medical center., Methods: Demographics, clinical data, and sinonasal mucus were collected from patients with CRS presenting for surgical consideration over a 5-year period. A random forest model and linear regression were used to assess predictor variables for the 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomains. Enzyme-linked immunosorbent assays were used to measure substance P and tryptase in a subset of mucus samples to explore biological differences by sex., Results: In total, 520 patients were studied (mean age 48.3 years, 50.9% female). Males were older (50.1 vs 46.6 years, P = .008), had more polyp disease (48.2% vs 35.5%, P = .004), and had higher mean Lund-Mackay CT score (11.3 vs 9.5, P = .004). Females had a higher overall mean SNOT-22 (40.9 vs 46.9, P = .001) and higher scores in ear/facial, psychological, and sleep domains ( P < .01). Age, objective disease measures, and sex were top predictors for total SNOT-22. Neither mucus substance P or tryptase, alone or paired with sex, correlated with total SNOT-22. Analysis of mucus biomarkers by sex revealed correlation between mucus tryptase in females with the extranasal subdomain ( P = .01)., Conclusion: Sex differences exist in CRS disease manifestations and presentation for surgical consideration. Detection of mucus (substance P and tryptase) was reliable, but in this exploratory study, we were not able to establish neurogenic or allergic inflammatory processes as a large source of differential disease features between sexes.

Background and Purpose: Sinus CT is critically important for the diagnosis of chronic rhinosinusitis. While CT is sensitive for detecting mucosal disease, automated methods for objective quantification of sinus opacification are lacking. We describe new measurements and further clinical validation of automated CT analysis using a convolutional neural network in a chronic rhinosinusitis population. This technology produces volumetric segmentations that permit calculation of percentage sinus opacification, mean Hounsfield units of opacities, and percentage of osteitis., Materials and Methods: Demographic and clinical data were collected retrospectively from adult patients with chronic rhinosinusitis, including serum eosinophil count, Lund-Kennedy endoscopic scores, and the SinoNasal Outcomes Test-22. CT scans were scored using the Lund-Mackay score and the Global Osteitis Scoring Scale. CT images were automatically segmented and analyzed for percentage opacification, mean Hounsfield unit of opacities, and percentage osteitis. These readouts were correlated with visual scoring systems and with disease parameters using the Spearman ρ ., Results: Eighty-eight subjects were included. The algorithm successfully segmented 100% of scans and calculated features in a diverse population with CT images obtained on different scanners. A strong correlation existed between percentage opacification and the Lund-Mackay score ( ρ = 0.85, P  < .001). Both percentage opacification and the Lund-Mackay score exhibited moderate correlations with the Lund-Kennedy score ( ρ = 0.58, P  < .001, and ρ = 0.58, P  < .001, respectively). The percentage osteitis correlated moderately with the Global Osteitis Scoring Scale ( ρ = 0.48, P  < .001)., Conclusions: Our quantitative processing of sinus CT images provides objective measures that correspond well to established visual scoring methods. While automation is a clear benefit here, validation may be needed in a prospective, multi-institutional setting., (© 2022 by American Journal of Neuroradiology.)

Importance: The distance traveled by patients for medical care is associated with patient outcomes (ie, distance bias) and is a limitation in outcomes research. However, to date, distance bias has not been examined in rhinologic studies., Objective: To evaluate the association of distance traveled by a cohort of patients with chronic rhinosinusitis with baseline disease severity and treatment outcomes., Design, Setting, and Participants: A total of 505 patients with chronic rhinosinusitis were prospectively enrolled in a multi-institutional, cross-sectional study in academic tertiary care centers between April 2011 and January 2020. Participants self-selected continued appropriate medical therapy or endoscopic sinus surgery. The 22-item Sinonasal Outcome Test (SNOT-22) and Medical Outcomes Study Short Form 6-D (SF-6D) health utility value scores were recorded at enrollment and follow-up. Data on the distances traveled by patients to the medical centers, based on residence zip codes, and medical comorbid conditions were collected., Exposures: Distance traveled by patient to obtain rhinologic care., Main Outcomes and Measures: SNOT-22 and SF-6D scores. Scores for SNOT-22 range from 0 to 110; and for SF-6D, from 0.0 to 1.0. Higher SNOT-22 total scores indicate worse overall symptom severity. Higher SF-6D scores indicate better overall health utility; 1.0 represents perfect health and 0.0 represents death., Results: The median age for the 505 participants was 56.0 years (IQR, 41.0-64.0 years), 261 were men (51.7%), 457 were White (90.5%), and 13 were Hispanic or Latino (2.6%). These categories were collected according to criteria described and required by the National Institutes of Health and therefore do not equal the entire cohort. Patients traveled a median distance of 31.6 miles (50.6 km) (IQR, 12.2-114.5 miles [19.5-183.2 km]). Baseline (r = 0.00; 95% CI, 0.00-0.18) and posttreatment (r = 0.01; 95% CI, -0.07 to 0.10) SNOT-22 scores, as well as baseline (r = -0.12; 95% CI, -0.21 to -0.04) and posttreatment (r = 0.07; 95% CI, -0.02 to 0.16) SF-6D scores, were not associated with distance. There was no clinically meaningful correlation between distance traveled and mean comorbidity burden. Nevertheless, patients with a history of endoscopic sinus surgery were more likely to travel longer distances to obtain care (Cliff delta = 0.28; 95% CI, 0.19-0.38)., Conclusions and Relevance: Although this cross-sectional study found that some patients appear more willing to travel longer distances for chronic rhinosinusitis care, results suggest that distance traveled to academic tertiary care centers was not associated with disease severity, outcomes, or comorbidity burden. These findings argue for greater generalizability of study results across various cohorts independent of distance traveled to obtain rhinologic care., Trial Registration: ClinicalTrials.gov Identifier: NCT02720653.

Chronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences., Objective: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs)., Methods: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures., Results: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells., Conclusion: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) improves pulmonary health and chronic rhinosinusitis (CRS) for people with cystic fibrosis (PwCF), however its impact on olfaction has not been investigated. Olfactory dysfunction impairs quality-of-life (QOL). This study evaluated the impact of ETI on multiple olfactory metrics., Methods: Adult PwCF/CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. Endpoints included changes after 6 months of ETI in quantitative olfactory function (Smell Identification Test, SIT), olfactory QOL (Questionnaire of Olfactory Disorders, QOD) and percent olfactory cleft opacification (%OCO), representing superior nasal cavity inflammation where afferent olfactory neurons are concentrated., Results: 30 PwCF/CRS met inclusion criteria; 25 completed the study. Mean ETI adherence was 93%. At baseline, participants were hyposmic (mean SIT 31.3), had significant %OCO (mean 65.6%), yet reported non-impaired olfactory QOL (mean QOD 6.1). At follow-up, mean SIT worsened mildly (p=0.009), mean %OCO remained stable (p=0.46), and mean QOD improved modestly (p=0.008). No outcomes were impacted by prior modulator use, genotype, nasal polyps, or CF-related diabetes. Prior sinus surgery was associated with QOD improvement (p=0.04). Increased (worse) baseline QOD scores and %OCO were associated with greater improvements (p<0.003), but not SIT (p=0.44)., Conclusions: ETI was not associated with improvement in quantitative olfaction or olfactory cleft opacification after 6 months. PwCF/CRS have hyposmia but do not report impairment in olfactory QOL. Further study to investigate mechanisms explaining olfactory dysfunction and whether olfaction improves with greater duration of ETI or in younger age groups is warranted., Competing Interests: Declaration of Competing Interest DMB: Medtronic, consultant, not affiliated with this work; SMH: Boehringer Ingelheim, Parexel and Imidex, consultant not affiliated with this work; CDB: none; MS: none; EKV: none; VRR: Medtronic and Optinose, consultant, not affiliated with this work; JLTC: received grants from Vertex Pharmaceuticals Incorporated, Gilead, N30, Celtaxsys, Proteostasis, and Bayer; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design, participation on advisory boards, and speaking engagements; has received speaking fees from Celtaxsys; and has served on advisory boards and/or provided consultation for Novartis, Genentech, Gilead, Protalix, Santhera, 4DMT, Abbvie and Proteostasis., (Copyright © 2021. Published by Elsevier B.V.)

Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Flowering in angiosperms is a crucial event that marks the transition from the vegetative to the reproductive phase. In many perennials, pruning is an important horticultural practice that induces synchronized and profuse flowering. In pomegranate, vegetative growth immediately after pruning is associated with activation of PgCENa, a flowering suppressor of the phosphatidyl ethanolamine binding protein (PEBP) family, while a reduction is associated with synchronous flowering. We show that flowering in pomegranate is activated by expression of another PEBP family member, PgFT1, a homolog of the FLOWERING LOCUS T (FT) gene that promotes flowering. PgFT1 shows a rapid reduction in expression during the extensive vegetative growth immediately after pruning but shows robust expression during synchronous flowering post-pruning, in flower-bearing shoots but not in branches that do not bear flowers. A continuous low-level flowering in the absence of pruning is associated with continuous but reduced expression of PgFT1. Flowering by heterologous expression of PgFT1 in Arabidopsis is affected by a single amino acid change in the C-terminal region of PgFT1, which upon correction, promotes flowering in Arabidopsis. Our study provides insights into the molecular mechanisms by which pruning affects flowering pathways in tropical perennial fruit plants such as pomegranate., (© 2022 Scandinavian Plant Physiology Society.)

Background: The impact of multiple coexisting medical comorbidities on treatment outcomes in chronic rhinosinusitis (CRS) is unknown. In this study we sought to evaluate the effect of comorbidities on sinonasal quality of life (QOL) and general health utility values by utilizing the Functional Comorbidity Index (FCI) in CRS patients., Methods: Patients with CRS were prospectively enrolled in a cross-sectional study of medical and surgical therapies. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Medical Outcomes Study Short-Form 6D (SF-6D) scores were recorded at enrollment and 6-month follow-up; Lund-Kennedy endoscopy and Lund-Mackay computed tomography scores were recorded at enrollment. The FCI was calculated using the electronic medical record. The impact of cumulative comorbidity burden on baseline and posttreatment outcomes was assessed using univariate and bivariate correlations., Results: A total of 428 participants with CRS were included. The average (mean standard ± deviation) FCI score was 3.03 ± 2.28 (range, 0-12). Significant linear correlations were identified between increasing FCI score and baseline SNOT-22 and SF-6D scores (R = 0.166, p = 0.001 and R = -0.245, p < 0.001, respectively). There was no correlation between FCI and change in SNOT-22 or SF-6D scores after CRS treatment (R = 0.066, p = 0.17 and R = -0.087, p = 0.074, respectively). Achievement of a minimally clinically important difference was also independent of FCI., Conclusion: Although cumulative comorbidity burden, as measured by FCI, is associated with worse baseline SNOT-22 and SF-6D scores, it does not appear to limit posttreatment improvement in either outcome measure. On average, patients with high comorbidity burden report substantial improvement in both QOL and health utility after CRS treatment, similar to those with fewer comorbidities., (© 2021 ARS-AAOA, LLC.)

Background: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated., Methods: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling., Results: Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19)., Conclusions: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings., (© 2021 ARS-AAOA, LLC.)

Hypermature cataracts with liquified cortex pose a higher risk for capsular complications due to a distended capsular bag, floppy posterior capsule, and absence of any cushioning epinucleus. Disassembly of a brunescent nucleus is more difficult because of the thickened, leathery posterior plate. Relying on mechanical forces, miLOOP nucleotomy reduces ultrasound time and is assured of bisecting the posterior nuclear plate. However, using this instrument with brunescent nuclei might impart significant stress on the zonular fibers and posterior capsule, particularly if there is no epinuclear shell. Evacuating the liquefied cortex and prolapsing one nuclear pole through capsulorhexis with ophthalmic viscosurgical devices create enough space to implant an intraocular lens (IOL) into the capsular bag beneath the undivided nucleus. This IOL scaffold shields the floppy posterior capsule and stabilizes the nucleus and zonular fibers during miLOOP nucleotomy. Combining and piggybacking these 2 techniques successfully avoided capsular and corneal complications in a series of 32 cases., (Copyright © 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample., Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey., Results: EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD., Conclusion: The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS., (© 2021 ARS-AAOA, LLC.)

Background: Multiple hypotheses are evolving that suggest several, potentially overlapping etiologies for olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). Understanding inflammatory cytokine profiles of the olfactory cleft (OC) and their association with olfactory function is foundational for future clinical care and research., Methods: This cross-sectional, case-control study evaluates associations among OC mucus inflammatory proteins, psychophysical olfactory testing, and computed tomography (CT) analysis of the OC and sinuses. Normative reference intervals were determined for each protein and odds ratios (ORs) were used to compare proportions of altered expression between CRS without nasal polyposis (CRSsNP) and CRS without nasal polyposis (CRSwNP)., Results: Case subjects with CRS (n = 151) and controls (n = 74) were evaluated. A majority of OC proteins tested were found within detectable ranges for cases and controls. The CRS cohort had significantly higher concentrations for 23 of 26 proteins. CRS cases with abnormal levels of C-C motif chemokine ligand 2 (CCL2), CCL3, interleukin 5 (IL5), IL10, and IL13 associated with greater olfactory deficits. The prevalence of elevated IL5 and IL13 in anosmic patients was 64.6% and 62.5%, respectively (p < 0.004). CRS cases with the highest odds of elevated expression in CRSwNP were IL5 (OR = 10.83) and IL13 (OR = 8.36). However, both IL5 and IL13 were still elevated in approximately 14% of CRSsNP patients. The highest magnitude of correlation between the total percent of OC opacification was found to be with IL5 (r = 0.543; p < 0.001), whereas other moderate correlations were noted with immunoglobulin E (IgE), IL10, and IL13., Conclusion: This study confirmed that OC inflammatory proteins vary both by disease phenotype and in their association with OD. Type 2 inflammatory mediators are increased in CRS, especially within the CRSwNP group. However, a substantial proportion of CRSsNP also express type 2 inflammatory mediators. Further research is necessary to understand the complex roles OC mucous inflammatory proteins might play in defining endotype and in impacting CRS-related OD. ©2021 ARSAAOA, LLC., (© 2021 ARS-AAOA, LLC.)

Background: Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient-reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient-reported outcome measures (PROMs)., Methods: Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient-reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22-item Sino-Nasal Outcome Test (SNOT-22)., Results: Thirty-six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow-up 9.6 ± 7.7 months. Mean PSQI and SNOT-22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT-22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1)., Conclusion: In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient-reported sleep quality and CRS-specific QOL., (© 2020 ARS-AAOA, LLC.)

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects., (© 2021 ARS-AAOA, LLC.)

Background: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss., Objectives: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach., Methods: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters., Results: A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/T h 17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ 18 2 =178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all)., Conclusions: Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Many patients with chronic rhinosinusitis (CRS) have persistent olfactory dysfunction (OD) following endoscopic sinus surgery (ESS). Few studies compare outcomes to control subjects so it is unknown if residual OD is due to persistent CRS., Objective: Compare postoperative measures of OD in case patients with CRS to healthy controls without sinonasal disease., Methods: Prospective, observational, multicenter cohort study between October, 2016 and May, 2019. Case participants were selected from referred adult patients diagnosed with CRS, with or without nasal polyposis (NP), electing ESS as subsequent treatment modality. Controls voluntarily enrolled from a community-based sample without a history of CRS. Primary outcomes included measures of preoperative and postoperative OD using "Sniffin' Stick" pens which summarize odorant threshold (T), discrimination (D), and identification (I) scores. Secondary outcomes included the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) survey and olfactory cleft endoscopy scores (OCES)., Results: Outcomes were compared between 113 cases and 164 controls of similar average age and gender. Cases reported significantly worse baseline Sniffin' Sticks TDI total scores (-6.8[SE ± 1.0]; 95% CI: -4.9 to -8.7), QOD-NS (8.9[SE ± 1.1]; 95% CI: 6.8-10.9), and OCES (3.5[SE ± 0.4]; 95% CI: 2.9-4.2) on average. Cases reported significant postoperative improvement in TDI total score (3.7[SD ± 8.2]; 95% CI: 2.2-5.2), QOD-NS (-5.9[SD ± 8.7]; 95% CI: -7.6 to -4.3), and OCES (-1.7[SD ± 3.8]; 95% CI: -2.7 to -0.8) on average, while 63% of anosmics reported improved postoperative olfaction. Multivariate regression identified that NP (OR = 0.4; 95% CI: 0.2-1.0) and previous ESS (OR = 0.3; 95% CI: 0.1-0.8) decreased the odds of postoperative improvement equal to mean TDI scores of controls, while septoplasty increased those odds (OR = 4.5; 95% CI: 1.5-13.7)., Conclusion: ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.

Background: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD)., Objective: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists., Methods: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD., Results: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction., Conclusions: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)